Water purification pack

ABSTRACT

An apparatus and methods are disclosed for purifying fluid, such as potable water, to quality levels suitable for medical application, particularly to applications involving injection of the fluid into a human body. The apparatus comprises a portable purification pack constructed for a single use. The pack houses depth filtration, activated carbon, mixed bed ion exchange resins and terminal filtration stages in series. The terminal filter comprises a fine (microfiltration or ultrafiltration), permeable membrane, treated with an endotoxin-binding chemistry. In contrast with semi-permeable osmotic membranes, the permeable membrane produces high flow rates at relatively low pressures, while still safely purifying fluid to injection quality.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of U.S. application Ser. No.09/277,448 filed Mar. 26, 1999, now U.S. Pat. No. 6,274,103.

FIELD OF THE INVENTION

The invention generally relates to water purification, and moreparticularly to devices and methods for purifying water to a qualitysuitable for medical applications.

BACKGROUND OF THE INVENTION

Various medical conditions require treatments that call for theinjection of fluids into the human body. For example, severe trauma tothe human body often involves significant loss of bodily fluids.Additionally, illnesses often cause diarrhea followed by dehydration andion imbalance. In order to rehydrate the individual, injection of anintravenous saline or dextrose solution is required. Other medicalapplications (e.g., wound irrigation) require similar fluid puritylevels.

An example of the need for injection of fluids into the body is in thearea of dialysis. Treatments for patients having substantially impairedrenal function, or kidney failure, are known as “dialysis.” Either blooddialysis (“hemodialysis”) or peritoneal dialysis methods may beemployed. Both methods essentially involve the removal of toxins frombody fluids by diffusion of the toxins from the body fluids into a toxinfree dialysis solution. Peritoneal dialysis can be performed withoutcomplex equipment and in a patient's home. In the peritoneal dialysisprocess, the patient's peritoneal cavity is filled with a dialysatesolution. Dialysates are formulated with a high concentration of thedextrose, as compared to body fluids, resulting in an osmotic gradientwithin the peritoneal cavity. The effect of this gradient is to causebody fluids, including impurities, to pass through the peritonealmembrane and mix with the dialysate. By flushing the dialysate from thecavity, the impurities can be removed.

Due to indirect contact with bodily fluids through bodily tissues,rather than direct contact with blood, the dextrose concentration needsto be considerably higher in peritoneal dialysis than in hemodialysis,and the treatment is generally more prolonged. Peritoneal dialysis maybe performed intermittently or continuously. In an intermittentperitoneal dialysis (IPD) procedure, the patient commonly receives twoliters of dialysate at a time. For example, in a continuous ambulatoryperitoneal dialysis (CAPD) procedure, the peritoneal cavity is filledwith two liters of dialysate and the patient is the free to move aboutwhile diffusion carries toxins into the peritoneal cavity. After about4-6 hours, the peritoneum is drained of toxified dialysate over thecourse of an hour. This process is repeated two to three times per dayeach day of the week. Continuous Cycle Peritoneal Dialysis (CCPD) incontrast, involves continuously feeding and flushing dialysate solutionthrough the peritoneal cavity, typically as the patient sleeps.

Because peritoneal dialysates are administered directly into thepatient's body, it is important that the dialysis solution maintains thecorrect proportions and concentrations of reagents. Moreover, it isimpractical to formulate and mix dialysis solutions on site at thetypical location of administration, such as the patient's home.Accordingly, peritoneal dialysates are typically delivered to the siteof administration in pre-mixed solutions.

Unfortunately, dialysis solutions are not stable in solutions over time.For example, dextrose has a tendency to caramelize in solution overtime, particularly in the concentrations required in the peritonealdialysis context. To prevent such caramelization, peritoneal dialysissolutions are typically acidified, such as with hydrochloric acid,lactate or acetate, to a pH between 4.0 and 6.5. The ideal pH level fora peritoneal dialysate, however, is between 7.2 and 7.4. While achievingthe desired goal of stabilizing dextrose in solution, the pH ofacidified peritoneal dialysis solutions tends to damage the body'snatural membranes after extended periods of dialysis. Additionally, theuse of acidified peritoneal dialysates tends to induce acidosis in thepatient.

Bicarbonates introduce further instability to dialysis solutions. Themost physiologically compatible buffer for a peritoneal dialysate isbicarbonate. Bicarbonate ions react undesirably with other reagentscommonly included in dialysate solutions, such as calcium or magnesiumin solution, precipitating out of solution as insoluble calciumcarbonate or magnesium carbonate. These insolubles can form even whenthe reactants are in dry form. When occurring in solution, the reactionsalso alter the pH balance of the solution through the liberation ofcarbon dioxide (CO₂). Even in the absence of calcium or magnesium salts,dissolved sodium bicarbonate can spontaneously decompose into sodiumcarbonate and CO₂, undesirably lowering the solution's pH level.

Accordingly, a need exists for improved methods and devices forformulating solutions for peritoneal dialysis. Desirably, such methodsand devices should avoid the problems of non-physiologic solutions andincompatibility of dialysate reagents, and also simplify transportation,storage and mixing of such dialysates. One aspect of this problem is theneed for mechanisms for safely and completely mixing constituents ofdialysates in diluent at the point of administration. Another aspect ofthis problem is the need for producing injectable quality water or otherdiluent at the point of administration.

It is often advantageous to provide purified fluid independently ofother constituents in the injected fluid. In many situations,independent provision of purified water simplifies transport and storageof solution constituents. In the case of peritoneal dialysis, preparingdialysate solution from dry reagents and independently provided purewater also minimizes the time for which unstable solutions must bestored prior to administration. Similarly, many other unstable solutionsshould be prepared soon before administration, preferably at the site ofadministration.

On site purification of fluids is also advantageous in a number of othermedical applications, including intravenous injection, intramuscularinjection, orally administered fluids, wound irrigation, use ininstrument cleaning solutions, and general employment byimmuno-compromised individuals (e.g., AIDS patients, geriatrics, etc.).

While separating provision of injectable quality fluid from otherconstituents can simplify transportation and delay production ofunstable solutions, transporting purified water to the site ofadministration, even if produced and shipped separately from dryreagents, can represent considerable costs, as well as introducingopportunities for contamination. Transportation costs and contaminationare particularly problematic when fluids are to be administered outsideof a controlled hospital or clinic environment. Problems are evenfurther exacerbated in lesser-developed countries, such as in the Indiansubcontinent and Africa. Even in a hospital setting, the ability toconvert available water into injectable quality water on site can reducetransportation and storage costs as well as avoiding the risk ofcontamination during transportation and storage.

Therefore, a need exists for a method and apparatus that allowpreparation of injectable quality fluid from available fluid. Desirably,the apparatus should be transportable and convenient for on-site use inremote locations.

SUMMARY OF THE INVENTION

In satisfying the aforementioned needs, the embodiments described hereinprovide a portable apparatus and method for purifying fluid to levelssuitable for medical applications, including injection into the humanbody.

In accordance with one aspect of the present invention, a portableapparatus is provided for producing injectable quality fluid. Theapparatus includes a housing that defines a fluid flow path from aninlet port to an outlet port. A depth filtration stage, an organicfiltration component, a deionization resin bed and a permeable membraneare held within the housing along the fluid flow path. The permeablemembrane has a porosity of less than about 0.5 μm and is configured toretain endotoxins.

In accordance with another aspect of the present invention, a waterpurification pack for producing injectable quality water includes acontainer. The container defines a flow-through path from an inlet to anoutlet with an average cross-sectional area of less than about 20 squareinches. The container houses purification elements within the path,including a permeable membrane having a porosity of no more than about0.5 μm. The purification elements provides a back-pressure low enough toallow fluid flow greater than about 30 mL/min under a feed pressure ofbetween about 5 psi and 10 psi.

In accordance with another aspect of the invention, a method is providedfor producing injectable quality of water. The method includes providinga portable purification pack with a housing surrounding purificationelements in series. Non-sterile water is provided to an inlet of thehousing under a feed pressure of less than about 20 psi. The waterpasses through the purification elements. Purified water exits from anoutlet of the housing. The purified water has an organic content,conductivity, pH level and particulate contamination level suitable forinjection into the human body.

In accordance with another aspect of the invention, a method is providedfor producing fluid for medical applications. The method includesproviding a portable housing. Non-sterile fluid passes through thehousing. Particulate contamination, organic matter, dissociated ions,microbes and endotoxins from the feed fluid are retained withinpurification elements in the housing. Fluid suitable for medicalapplications is then output from the housing.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects of the invention will be apparent to the skilledartisan in view of the Detailed Description and claims set forth below,and in view of the appended drawings, which are meant to illustrate andnot to limit the invention, and wherein:

FIG. 1 is a schematic side perspective view of a system for producingperitoneal dialysate or other medical solutions;

FIG. 2 is a schematic side sectional view of a fluid purification pack,constructed in accordance with one aspect of the present invention;

FIG. 3 is a schematic side sectional view of a reagent cartridge forhousing reagents of peritoneal dialysate;

FIG. 4 shows the reagent cartridge of FIG. 3 after partial dissolutionof the reagents housed therein;

FIG. 5 shows the reagent cartridge of FIG. 3 after complete dissolutionof the reagents housed therein;

FIG. 6 is a schematic side sectional view of a reagent cartridge forhousing reagents of peritoneal dialysate;

FIG. 7 shows the reagent cartridge of FIG. 6 after complete dissolutionof the reagents housed therein;

FIGS. 8A and 8B illustrate side sectional and plan views, respectively,of a downstream end of the water purification pack of FIG. 2;

FIGS. 9A and 9B illustrate side sectional and plan views, respectively,of an upstream end of the reagent cartridge of FIG. 3, configured toirreversibly connect with the water purification pack; and

FIG. 10 is a side sectional view of a coupling between the waterpurification pack and reagent cartridge of FIGS. 8 and 9.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

While the illustrated embodiments are described in the context of aparticular application, i.e., peritoneal dialysis, the skilled artisanwill find application for the apparatus and methods for producinginjectable quality fluid in a variety of medical applications. Moreover,the apparatus and methods for producing “injectable quality” fluids willhave applications beyond the medical field, wherever similarly purewater is desirable. The fluid purification unit described herein hasparticular utility when connected in series upstream of fluidcollection/delivery devices, such as the illustrated mechanism formixing dry reagent as purified diluent flows through.

System for Preparing Peritoneal Dialysis Solution

FIG. 1 illustrates a system 10 for producing solutions suitable forinjection into the human body. A diluent or fluid purification pack 12,as described in more detail below, is connected upstream of a reagentcartridge 14. The cartridge 14, in turn, is in fluid communication witha solution reservoir 16 via a tube 18. As also set forth in more detailbelow, purified diluent is provided from the pack 12 to the reagentcartridge 14, wherein the dry reagents are dissolved and solution isdelivered to the reservoir 16. Alternatively, the solution can bedelivered directly to the patient's body.

In the illustrated embodiment, the solution comprises peritonealdialysis solution. The cartridge 14 advantageously houses dry orlyophilized formulations of reagents suitable for peritoneal dialysis.Desirably, the solution is formed immediately prior to delivery to thepatient's peritoneal cavity, such that the dialysate need not be storedin solution form for extended periods, and little opportunity existsundesirable reactions within the solution prior to delivery.

The cartridge 14 defines fluid flow paths through the dry reagents, byway of porous elements therebetween, enabling dry storage in confinedreagent beds while also enabling dissolution simply by passing diluentthrough the housing. Two preferred versions of the cartridge 14 aredescribed in more detail with respect to FIGS. 3-7, below.

The diluent purification pack 12 of the illustrated embodiment iscapable of on-site purification of locally available fluid, such as tapwater from a municipal water source. The preferred water purificationpack is described in more detail with respect to FIG. 2 below.

Water Purification Pack

Referring to FIG. 2, the preferred fluid purification pack 12 is capableof purifying water or other liquid diluent to the standards required forinjection into a patient, e.g., for peritoneal dialysis applications.Advantageously, available water, preferably potable water, can beintroduced to the system, and is purified as it flows through the pack.The purified water can be delivered, for example, directly to thereagent cartridge 14 (FIG. 1), to a storage or collection container forshort-term storage or transportation or direct connection to lineanother delivery device, such as a wound irrigation pump. Accordingly,bulky purified water need not be stored long in advance of its need ortransported great distances to the point of administration. Complexmachinery for purifying water is also obviated.

In order to serve as a diluent for injection into the human body, or forsimilar applications, the independently provided water must be highlypurified. The U.S. Pharmacopoeia provides processes for producingsterile water for injection. The preferred water pack 12 also produceswater of a quality suitable for injection, preferably equivalent to orsurpassing the quality produced by the U.S. Pharmacopoeia processes.Water purified through the pack thus preferably meets or exceeds theU.S. Pharmacopoeia's standards for Sterile Water for Injection,including sterility, pH, ammonia, calcium, carbon dioxide, chloride,sulfate and oxidizable substances tests. In particular, injectablequality water or other fluid produced by the illustrated waterpurification pack 12 exhibits the following characteristics: a very lowlevel of total organic carbon, preferably less than about 1 ppm and morepreferably less than about 500 ppb; low conductivity, preferably lessthan about 5.0 μSiemens (2.5 ppm) and more preferably less than about2.0 μSiemens (1 ppm); near neutral pH, preferably between about 4.5 and7.5, and more preferably between about 5.0 and 7.0; very low particulateconcentration, preferably fewer than less than about 12 particles/mL ofparticles ≧10 μm, more preferably less than about 6 particles/mL of suchparticles, and preferably less than about 2 particles/mL of particles≧25 μm, more preferably less than about 1 particle/mL of such particles;and low endotoxin levels, preferably less than about 0.25 endotoxinunits (EU) per mL (0.025 ng/mL), more preferably less than about 0.125EU/mL (0.0125 ng/mL) with a 10:1 EU/ng ratio.

Conventionally, purifying non-sterile fluid to such stringent qualitystandards, particularly for introduction into the human body, has calledfor extensive mechanical filtration and/or distillation, pumping,distribution and monitoring systems. These complex mechanisms can safelyand economically produce large volumes of sterile water to injectablequality. Such mechanisms, however, occupy considerable space at acentral location and necessitate even more space for storing purifiedwater closer to the site of administration. Moreover, conventional waterpurification mechanisms are not conducive to employment in a portableapparatus for use in the field.

U.S. Pat. No. 5,725,777 to Taylor discloses a portable apparatus forpurifying water to injectable quality. The apparatus includes severalstages for purification, including multistage depth prefiltering,ultrafiltration fibers, reverse osmosis fibers, ion exchange resin andactivated carbon in that order.

The reverse osmosis stage of Taylor '777 effectively purifies water to ahigh degree. Unfortunately, because reverse osmosis involves diffusinginput water across a semi-permeable membrane, the rate of waterproduction is very slow relative to the cross-section of the membrane.Even with the use of multiple reverse osmosis fibers with a high overallmembrane surface area, diffusion is slow. In order to fully realize theadvantages of portability, purified diluent should be rapidly producedat the time of administration. For acceptable rates using the apparatusof Taylor '777, however, high pressures (e.g., 40 to 75 psi) are appliedacross the semi-permeable membrane. Pumps and restrictor means forrealizing these pressures reduce the versatility and portability of theoverall system.

In the illustrated embodiment, the water or fluid purification pack 12comprises a housing 20 with an axial inlet 22 and outlet 24. The housing20 defines a flow path between the inlet 22 and outlet 24, with multiplepurification stages along the flow path. The pack 12 is thus designed topurify fluid in the course of traveling, preferably in a linear path,through the housing 20.

The housing 20 is preferably formed of a suitable polymer, particularlypolycarbonate, which aids in purifying water by binding endotoxinsthrough charge interactions. Endotoxins are the organic byproduct ofdead microorganisms, particularly the outer cell wall of bacteria.Although the term endotoxin is occasionally used to refer to any“cell-associated” bacterial toxin, it primarily refers to thelipopolysaccharide complex associated with the outer envelope ofGram-negative bacteria such as E. coli, Salmonella, Shigella,Pseudomonas, Neisseria, Haemophilus, and other leading pathogens. Inhigh enough concentrations, particularly in critical applications suchas intravenous injection, this organic matter can be toxic.

The pack 12 is configured for convenient, handheld portability. Theskilled artisan will appreciate the fact that different sizes willsafely produce different amounts of purified water. Thus, for anembodiment optimized for safely purifying 10 L of water, the outsidedimensions of the housing 20 preferably include a length of less than orequal to about 6 inches from inlet 22 to outlet 24, and a width(diameter in the illustrated embodiment) of less than or equal to about5 inches. The illustrated housing 20, designed for safely purifying 2 Lof water, has a length of about 3 inches and a diameter of about 2.25inches. Preferably, therefore, the fluid purification pack 12 has across-sectional area of less than about 20 sq. inches, more preferablyless than about 4 sq. inches. Despite this small cross-section, theillustrated pack 12 can achieve high flux rates under pressures as lowas about 5-10 psi.

The fluid purification pack 12 is also preferably configured to delivera unit dose of purified fluid. The pack 12 thus is preferably designedfor one-time use and to be discarded thereafter. As such, the sterilityof the pack 12 can be assured, since the pack 12 will not be reusedafter seals at the inlet 22 and outlet 24 are broken. Several of thefeatures described hereinbelow discourage or prevent recharging thewater pack 12 for repeated use, as will be understood by the skilledartisan.

Downstream of the inlet 22 is a depth filter 26. The porosity limit ofthe illustrated depth filter 26 preferably ranges from about 1 micron(μm) to 10 μm, most preferably about 1 μm. The depth filter 26 ispreferably formed of a porous polypropylene mesh in multiple layers,particularly two to four layers. Alternatively, the commerciallyavailable celluose-based depth filters can be employed, as will beunderstood by one of ordinary skill in the art. In still otherarrangements, ceramic or other known particle filtration material can beemployed. Most preferably, the depth filter 26 comprises a series ofdepth filters (not shown) that successively filter out smaller andsmaller particles. In the illustrated embodiment, four successive depthfilters are included within the depth filtration stage 26, havingporosities of about 100 μm, 40 μm, 10 μm and 1 μm in sequence fromupstream end to downstream end.

Downstream of the depth filter 26 is an organic filtration stage 28,which can comprise a bed of granular carbon. In the illustratedembodiment, the organic filtration stage comprises a resin bed treatedfor retention of organic contaminants. The illustrated embodimentincorporates a form of styrene divinylbenzene commercially availablefrom Rohm & Haas of Philadelphia, Pa. under the trade names Ambersorb563. This component removes certain residual organic contaminants, suchas endotoxins, as we as commonly used additives placed in municipallytreated waters (e.g., chlorine, trihalomethanes and chloramine).

Adjacent to the downstream end of the organic filtration stage 28 is arestraint 30. The restraint 30 is a filter of controlled porosity,preferably also comprising a polypropylene mesh with a porosity of about1-10 microns, more preferably about 1 micron. This component preventspassage of particulates shed by the organic filtration component 28, aswell as providing a secondary assurance that insoluble particulates donot pass further through the water purification pack.

Adjacent to the downstream side of the restraint 30 is a deionizationstage, preferably comprising a bed 32 of deionization resin beads. Theresin bed 32 more preferably comprises a mixture of pharmaceutical graderesins with strong anion exchanger (cation-impregnated) and strongcation exchanger (anion-impregnated) chemistries, binding dissociableions and other charged particles with a very high affinity. In theillustrated embodiment, the resin bed 32 comprises mixed anion- andcation-impregnated resin beads with weakly associated hydrogen orhydroxy groups, respectively. The ion exchange resins of the preferredembodiment comprise styrene divinyl benzene. Such resins are available,for example, from Rohm & Haas of Philadelphia, Pa. under the trade nameIRN 150, or from Sybron of Birmingham, N.J. under the trade name NM60.Cation exchangers exchange hydrogens for any dissolved cations in thediluent. Common dissolved cations include sodium (Na⁺), calcium (Ca²⁺)and aluminum (Al³⁺). The anion exchange resins exchange hydroxy ions forany anions present in an aqueous solution. Common anions includechloride (Cl⁻) and sulfides (S²⁻). The resin bed 32 additionally retainssome endotoxins that escape the upstream filtration components. Theskilled artisan will recognize other types of ion-exchange resins thatcould also be utilized in this stage.

The preferred mixed resin bed 32 simplifies and provides a more compactpack 12 than more conventional ion exchange columns, wherein anion andcation exchangers are separated. Moreover, the mixed bed 32 arrangementprevents recharging the ion exchange resin by back-flushing, thusdiscouraging re-use and maintaining sterility of the unit.

Downstream of the deionization resin bed 32 are a deionization bedrestraint 34 and a terminal filter element 36, in sequence. Therestraint 34 preferably comprises the same polypropylene mesh utilizedfor the illustrated depth filter 26 and carbon bed restraint 30. Theresin bed restraint 34 serves to prevent passage of deionization bedfragments or fines, as well as any other particulates that have escapedthe upstream filters 26, 30. The restraint 34 also serves to protect thefilter element 36 downstream of the restraint 34.

The terminal filter element 36 comprises a permeable membrane,preferably a microfiltration or ultrafiltration membrane, depending uponthe application. The term “terminal,” as utilized in this context,refers to the filtration element with the lowest porosity, and not thephysical location. Typically, however, the terminal filter will beimmediately adjacent the outlet, as shown, such that large particulatesare filtered out by courser filtration elements upstream of the terminalfilter. The terminal filter 36 preferably has a porosity of at mostabout 0.5 μm, and none preferably less than about 0.22 μm.

For applications in remote locations where water is untreated orinsufficiently treated, an ultrafiltration membrane is most preferable.Nominal porosity of between about 10,000 and 30,000 molecular weightcut-off desirably filters out viruses prevalent in such locations, suchas hepatitis, rota virus, polio, etc. Nominal cut-off for theillustrated embodiment is between about 15,000 and 25,000 MW. Whileendotoxins (complex lipopolysaccaride) generally aggregate intocomplexes of greater than about 1,000,000 molecular weight, anultrafiltration membrane can retain even a single unit of endotoxin(about 15,000 molecular weight).

For employment in more developed locations, where treated water isavailable (e.g., municipal water in most American cities), the waterpurification pack 12 need not filter out pathogenic viruses.Accordingly, for such uses the terminal filter 36 comprises amicrofiltration membrane. Advantageously, the higher porosity of amicrofiltration membrane allows a greater flow rate for a given feedpressure or a lower feed pressure for a given flow rate. Themicrofiltration membrane preferably has a porosity of lower than about0.5 μm, and more preferably comprises a 0.22 μm or finer filter, andmost preferably has a porosity of about 0.20 μm or finer. Desirably, theterminal filter 36 has enhanced endotoxin binding characteristics and ispreferably chemically treated to incorporate a quaternary amineexchanger (QAE) to bind endotoxins. Such endotoxin binding membranes areavailable under the trade name HP200 from the Pall Specialty MaterialsCo. Most preferably, the terminal filter 36 comprises two successiveQAE-treated 0.20 μm permeable membranes, ensuring adequate endotoxinretention. Despite a high flux rate compared to ultrafiltrationmembranes, therefore, the terminal filter 36 incorporating amicrofiltration membrane removes endotoxins as well as microbes andparticulate matter of less than 1 μm from diluent passing therethrough.In fact, challenge water with endotoxin levels as high as 1,000 ng/mLhave been purified through the illustrated pack 12 to below the currentdetection limit (0.006 ng/mL).

The purification stages within the water purification pack are thus suchthat water passing through the pack 12 and exiting the housing outlet 24is of a purity level safe for injection into the human body (followingthe addition of appropriate salts for physiologic solutions).Preferably, effluent water conforms to the purity levels set forthabove. It will be understood, of course, that while safe enough forinjection, the fluid may actually be employed for alternative medicalapplications, such as wound irrigation, use in instrument cleaningsolutions, and general employment by immuno-comprised individuals (e.g.,AIDS patients, geriatrics, etc.).

Desirably, the water purification pack 12 includes an upstream cap 38over the housing inlet 22, and a downstream cap 40 over the housingoutlet 24. The sterility of the purification elements housed within thehousing 20 is thus maintained until use. As will be understood in theart, the inlet 22 and outlet 24 can be provided with threads orLuer-type fittings (see FIGS. 8-10) to mate with upstream and downstreamelements in the peritoneal dialysate delivery system 10 (FIG. 1).

The sterility and efficacy of the water purification pack 12 is alsoreinforced by features discouraging re-use of the water pack. Aspreviously noted, the resin bed 32 preferably comprises a mixed bed ofanion- and cation-exchangers. Thus, the mixed bed 32 cannot be rechargedby traditional backflushing techniques, since regeneration of thecation-exchanger would result in exhaustion of the anion exchanger andvice versa.

Additionally, the water purification pack is preferably configured toirreversibly connect with a downstream collection device. In onepreferred arrangement, the housing outlet 24 is welded or otherwiseintegrally connected with a collection tube leading to a collection bagor other container. When water is purified by passing through thehousing 22 and fills the downstream collection container, the preferredplastic tubing is simultaneously cut and cauterized to seal the tubedownstream of the outlet 24, preventing re-use of the water pack 12.

With reference to FIGS. 8 and 9, in another preferred arrangement, theoutlet 24 is irreversibly connectable with the downstream reagentcartridge 14. The water pack outlet 24 and the reagent cartridge inlet52 thus have interlocking mechanisms that are irreversible withoutdamage to the mechanisms.

In the illustrated embodiment, the water pack housing 20 includes acylindrical collar 42 surrounding the outlet 24, the collar having outerratcheting teeth 44. The reagent pack 14 includes a similar cylindricalcollar 46 surrounding the inlet 52, and the collar 46 includes internalratchet teeth 48. The outer collar 46 of the reagent pack 14 is sized tofit over the outer collar 42 of the water pack 12. The ratcheting teeth44, 46 are sloped to slide past each other during clockwise rotation totighten the inner Luer lock mechanism. The teeth 44, 46 engage oneanother, however, to prevent counter-clockwise rotation, such that theLuer lock cannot be loosened.

Accordingly, the locking mechanism must be broken or otherwise damagedto separate the used water pack 12 from the reagent cartridge 14. Suchdamage or breakage minimizes the risk of accidentally re-using a spentwater pack 12. The skilled artisan will readily appreciate that similarirreversible locking mechanisms can be utilized with other collection ordelivery devices downstream of the water purification pack. The skilledartisan will also recognize other suitable irreversible lockingmechanisms for discouraging re-use.

Single-Bed Reagent Cartridge

FIGS. 3-5 illustrate a single-bed reagent cartridge 14 for use with thewater purification pack. The figures illustrate various stages ofdissolution, as will be better understood from the methods of operationdiscussed hereinbelow.

FIG. 3 shows a fully charged reagent cartridge 14, in accordance withthe first embodiment. The cartridge 14 comprises rigid walled housing 50with an inlet port 52 at an upstream end, and an outlet port 54 at adownstream end. Within the housing, a number of porous elements define afluid flow path between the inlet port 52 and the outlet port 54.

The housing 50 is preferably transparent or translucent, advantageouslyenabling the user to observe the operation of the device and completedissolution of reagents prior to use of a produced solution, as will beapparent from the discussion of the method of operation, discussedhereinbelow. Examples of translucent and transparent polymers arepolypropylene, polycarbonate and many other well-known materials.

Within the housing 50, immediately downstream of the inlet port 52, isan inlet frit 56, which serves as a safety filter to contain any reagentwhich escapes the restraints described below. An outlet frit 58 serves asimilar function immediately upstream of the outlet 54. Desirably, theinlet frit 56 and the outlet frit 58 comprise porous elements having aporosity smaller than the smallest particle of the reagents housedwithin the cartridge 14. The frits 56, 58 thus serve as filters toensure that no reagent escapes the cartridge prior to dissolution, aswill be described below. An exemplary frit is a multilayeredpolypropylene laminate, having a porosity between about 1 μm and 100 μm,more preferably between about 10 μm to 50 μm. Further details on thepreferred material are given below, with respect to the reagentrestraints.

Downstream of the inlet frit 56 is an upstream reagent compressioncomponent 60. Similarly, upstream of the outlet frit 58 is a downstreamreagent compression component 62. The compression components 60, 62preferably comprise materials that have sponge-like elasticity and, as aresult of compression, exert axial pressure while trying to return toits original, expanded form. The compression components 60, 62preferably comprise compressible, porous, open cell polymer or foam,desirably more porous than the frits, to avoid generation of backpressure. An exemplary material for the compression components is apolyurethane foam. Desirably, the compression components 60, 62 andsurrounding housing 50 are arranged such that the compression components60, 62 exert a compressive force on the reagent bed regardless of thesize of the reagent bed. In other words, the compression components 60and 62 would, if left uncompressed, together occupy a greater volumethan that defined by the housing 50. Desirably, the pressure exerted isbetween about 50 grams per sq. inch and 2,000 grams per sq. inch, morepreferably between about 300 grams per sq. inch and 900 grams per sq.inch.

It will be understood that, in other arrangements, metal or polymercoiled springs and porous pates can serve the same function. Suchalternative compression components are disclosed, for example, withrespect to FIGS. 12-15; Col. 9, lines 8-53 of U.S. Pat. No. 5,725,777,the disclosure of which is incorporated herein by reference. Anotherpreferred compression component is disclosed in U.S. provisionalapplication No. 60/132,088, filed Apr. 30, 1999, the disclosure of whichis hereby incorporated by reference. It will also be understood, in viewof the discussion below, that a single compression component can servethe function of the illustrated two compression components. Twocomponents exerting pressure on either side of a reagent bed 64(described below), however, has been found particularly advantageous inoperation.

A single reagent bed 64 is situated between the compression components60, 62. The reagent bed 64 is desirably sandwiched between an upstreamreagent restraint 66 and a downstream reagent restraint 68. The upstreamreagent restraint 66 is thus positioned between the reagent bed 64 andthe upstream compression component 60, while the downstream reagentrestraint 68 is positioned between the reagent bed 64 and the downstreamcompression component 62.

The restraints 66, 68 desirably prevent the passage of reagent particlesin their dry formulation. The porosity of the restraints is thereforeselected to be less than the size of the smallest particles within thereagent bed, depending upon the particular reagent formulations andphysical particle size desired. Desirably, the pores are large enough toavoid excessive pressure drop across the restraints. Preferably, therestraint porosity in the range between about 1 μm and 100 μm, morepreferably between about 10 μm to 50 μm. An exemplary restraint,suitable for the illustrated peritoneal dialysis application, comprisesthe same material as the frits 56, 58, and consists of a non-wovenpolymer, particularly polypropylene with a porosity of about 20 microns.Another exemplary restraint comprises sintered polyethylene with aporosity of about 30 microns.

Additionally, the restraints 66, 68 are sized and shaped to extendcompletely across the housing 50, forming an effective seal againstreagent particulates escaping around the restraints 66, 68.

The reagent bed 64 comprises a complete formulation of dry orlyophilized reagents required to produce a peritoneal dialysis solution.In the illustrated single-bed embodiment, the reagent bed 65 is amixture of compatible reagents, such as will not exhibit spontaneouschemical reaction from prolonged contact in their dry form. Accordingly,a buffering agent such as an acetate or lactate, and particularly sodiumlactate, is employed in place of a bicarbonate. Further reagents includeelectrolytes, such as sodium chloride, magnesium chloride, potassiumchloride and calcium chloride; a sugar, preferably dextrose; and anacid, particularly citric acid. Advantageously, the acid component ofthe reagent bed 65 can be lower than conventional solutions, sincestorage in dry form alleviates the tendency for dextrose caramelization.

The illustrated housing 50 holds reagents sufficient to produce 2 litersof a typical peritoneal dialysate solution. Accordingly, the reagent bed64 holds the following reagents:

TABLE I Dry Reagent Constituents Mass Dry Volume Calcium chloride 514 mgNegligible Magnesium chloride 101.6 mg Negligible Sodium lactate 8.96 g24 mL Sodium chloride 10.76 g 22 mL Dextrose 50 g 70 mL Total 70 g 116mL

The dry volume of the above-listed reagents, which can produce 2 L of2.5% dextrose peritoneal dialysate, is thus about 100 mL. The housing 50for such a formulation need only be about 125% to 500% of the dryreagent volume, more preferably about 150% to 200%, depending upon theselected compression components 60, 62. The illustrated housing 50 isabout 2″ in diameter and about 3″ in height, thus occupying about 175mL. The cartridge 14 thus represents a much smaller and more stable formof dialysate for storage and transport, compared to 2 L of preparedsolution. If a smaller or larger volume of solution is desired, theskilled artisan can readily determine the proportionate weight andvolume of dry reagents required in the reagent bed 64, such as forproducing 1 L, 3 L, 6 L, 10 L, etc. Similarly, the skilled artisan canreadily determine the proportions of reagents desirable for 1.5%dextrose dialysate, 4% dextrose dialysate, etc.

An inlet port cover 70 and an outlet port cover 72 cover the housinginlet port 52 and outlet port 54, respectively. The port covers 70, 72advantageously seal out moisture and prevent destabilization of the dryreagents housed within during transport and storage. As with the waterpurification pack, the inlet port 52 and outlet port 54 can beconfigured with threaded or Luer-type connection fittings. In theillustrated embodiment, the inlet port 52 is configured to mate with theoutlet 24 of the water purification pack 12 (FIG. 2), while the outletport 54 is configured to mate with the downstream tube 18 (see FIG. 1).

Double-Bed Reagent Cartridge

FIGS. 6 and 7 illustrate a double-bed reagent cartridge 14′. FIGS. 6 and7 illustrate the cartridge 14′ in fully charged and fully depletedconditions, respectively, as will be better understood from the methodsof operation discussed hereinbelow.

With reference initially to FIG. 6, the housing 50 of the double-bedreagent cartridge 14′ is preferably similar to that of the firstembodiment, such that like reference numerals are used to refer to likeparts. Thus, the housing 50 defines an inlet port 52 and outlet port 54,and contains porous elements between the inlet port 52 and outlet port54, such as to define a fluid flow path through the housing 50.Specifically, the housing 50 contains an upstream frit 56, upstreamcompression component 60, upstream reagent restraint 66, downstreamreagent restraint 68, downstream compression component 62 and downstreamfrit 58. Each of these elements can be as described with respect to theprevious embodiment.

Unlike the single-bed cartridge 14 of FIGS. 3-5, however, multiplereagent beds are confined between the upstream restraint 66 anddownstream restraint 68. In particular, a primary reagent bed 80 and asecondary reagent bed 82 are shown in the illustrated embodiment,separated by at least one restraint. In the illustrated embodiment, thereagent beds 80 and 82 are separated by a first intermediate restraint84 and second intermediate restraint 86, as well as an intermediatecompression component 88 between the intermediate restraints 84 and 86.

Accordingly, the primary reagent bed 80 is confined between upstreamrestraint 66 and the first intermediate restraint 84, while thesecondary reagent bed 84 is similarly confined between the secondintermediate restraint 86 and the downstream restraint 68. Theintermediate reagent bed restraints 84, 86 desirably serve to containthe reagents within the beds 80, 82 in their dry form, while still beingporous enough to allow diluent, along with any dissolved reagents, topass through. Accordingly, the intermediate reagent restraints 84, 86can have the same structure as the frits 56, 58 and upstream anddownstream reagent restraints 66, 68, as described above with respect tothe single-bed embodiment. Similarly, the intermediate compressioncomponent 88 can have the same structure as the upstream and downstreamcompression components 60, 62.

Each of the intermediate compression component 88 and the intermediatereagent restraints 84, 86 are interposed between and separate theprimary reagent bed 80 from the second reagent bed 82. Due to theselected porosity of the elements, particularly the intermediaterestraints 84, 86, constituents of the two reagent beds 80, 82 thereforedo not interact with one another in their dry states.

The illustrated double-bed embodiment therefore enables separate storageof different reagents within the same housing 50. A complete formulationof the dry reagents required to produce a peritoneal dialysis solutionmay contain reagents that react undesirably when exposed to one otherfor prolonged periods of time, in either dry or liquid forms, as notedin the Background section. For example, bicarbonates are preferred,physiologically compatible buffering agents for peritoneal dialysis, buttend to be very reactive with typical salts in the dialysateformulation, such as calcium chloride or magnesium chloride. Thereactions form insoluble calcium carbonate or magnesium carbonate, andalso liberate CO₂. Because of the potential reactivity of incompatiblereagents, it is preferable to separately store these reagents within thedevice housing 50.

Separate storage is accomplished by separating reagents into compatiblegroupings, which are then placed in separate compartments within thehousing. The compartments are represented, in the illustratedembodiment, by the primary reagent bed 80 and the secondary reagent bed82. The potentially reactive reagents are thereby constrained frommovement through the housing, when maintained in their dry form, byreagent bed restraints 66, 84, 86, 68 at the upstream and downstreamends of each of the reagent beds 80, 82. As noted above, the reagent bedrestraints 66, 84, 86, 68 have fine enough porosity to prevent thepassage of reagent particles in their dry form.

In the illustrated embodiment, the primary reagent bed 80 is a reagentmixture, preferably comprising: electrolytes, particularly sodiumchloride, potassium chloride, calcium chloride and magnesium chloride; asugar, particularly dextrose. In other arrangements, the primary reagentbed 80 can also comprise a buffer.

The secondary reagent bed 82 can contain at least one component that isunstable in the presence of at least one component in the primaryreagent bed 80. Advantageously, the secondary reagent bed 82 contains abicarbonate, such as sodium bicarbonate. Because the bicarbonate isseparated from calcium chloride and magnesium chloride, the reagents donot react to form insoluble precipitates.

The skilled artisan will readily appreciate that, in other arrangements,the primary reagent bed 80 can contain the bicarbonate if the secondarybed 82 contains calcium chloride and/or magnesium chloride. In stillother alternatives, other incompatible reagents for medical solutionscan be similarly separated into reagent beds within the same housing.Moreover, three or more reagent beds can be utilized to separatemultiple incompatible reagents.

The illustrated housing 50 holds reagents sufficient to produce 2 litersof a typical peritoneal dialysate solution. Accordingly, the reagentbeds 80, 82 hold the following reagents:

TABLE II Mass Dry Volume Primary Reagent Bed Calcium chloride 514 mgNegligible Magnesium chloride 101.6 mg Negligible Sodium chloride 10.76g 22 mL Dextrose 50 g 70 mL Subtotal 61 92 mL Secondary Reagent BedSodium bicarbonate 6.64 g 6.1 mL Total 68 g 98 mL

The dry volume of the above-listed reagents, which can produce 2 L of2.5% dextrose peritoneal dialysate, is thus about 98 mL. As with thepreviously described single-bed embodiment, the total volume of thecartridge 14′ is preferably between about 125% and 500%, and morepreferably 150% and 200%, of the dry reagent volume. As also notedabove, the skilled artisan can readily determine the proportionateweights and volumes of dry reagents required for forming otherperitoneal dialysate solutions, such as 1.5% dextrose dialysate, 4%dextrose dialysate, etc.

Notably, the double-bed cartridge utilizes bicarbonate as the buffer,and omits the need for physiologically damaging acid by enablingproduction of a physiologic solution.

Method of Operation

In operation, purified diluent is provided to a reagent cartridge 14 or14′, which is fully charged with an appropriate amount of dry reagent,as set forth above. Fluid to be purified (e.g., municipal tap water) isprovided to the system 10 of FIG. 1, such that the purified diluent isproduced on site and need not be produced remotely and transported,significantly reducing the cost of transportation.

Accordingly, with reference to FIG. 2, diluent in the form of availablewater is first provided to water purification pack 12 of FIG. 2.Pressure commonly found in municipal water systems is sufficient to feedthe water through the purification pack 12. Alternatively, a hand pumpor large syringe can be supplied with a measured volume of water, andwater hand-pumped therefrom into the purification pack 12. Feed pressureis preferably less than about 20 psi. Fluid flux through thepurification pack 12 (with a feed pressure of about 5-10 psi) ispreferable at least about 30 mL/min, and more preferably at least about90 mL/min through the pack 12.

The diluent enters the inlet 22 and passes through depth filter 26,where particulates larger than about 1 micron are filtered out. Thedepth filter 26 retains insoluble particulates and microbes greater thanthe pore sizes of the successive layers in this component. Depthfiltration is extremely effective in removing contaminants such asasbestos fibers and similarly sized particles.

Filtered diluent continues downward through organic filtration stage 28,where residual organics such as endotoxins and additives such aschlorine, chloramine and trihalomethanes are adsorbed. Additionally,some inorganic materials are removed in the process. Carbon is effectiveat adsorbing many types of chemicals, it is especially known for itspower in adsorbing organic compounds. Carbon's particular affinity fororganics is due to its non-polar nature. Carbon is also somewhateffective in adsorbing metals and other inorganics. The illustratedresin has similar absorption characteristics.

After being additionally purified by the organic filtration stage 28,the partially purified diluent passes through the restraint 30 and intothe ion-exchange resin bed 32. Dissociated ions and other chargedparticulates in solution bind to the resins. Some endotoxins that haveescaped the upstream components are also retained in the resin bed 32.

After passing through the resin bed restraint 34, which retains thecontents of the resin bed 34, the diluent is further purified throughthe terminal filter element 36. In one embodiment, as previously noted,the terminal filter 36 comprises an ultrafiltration membrane with anominal cut-off of between about 10,000 and 30,000 molecular weight.Depending upon the density of pores, 5-10 psi feed pressure can producea flux of between about 35 mL/min and 100 mL/min through such anultrafiltration membrane. In another embodiment, the filter 36 comprisesat least one and preferably two microfiltration membranes of a very fineporosity (e.g., about 0.22 μm or finer), each including chemicaltreatment with a quaternary amine exchanger for binding residualendotoxins. The flux rate for a device with the microfiltration membranecan be more that twice that of an ultrafiltration membrane withequivalent pore density.

The multiple filtration and chemical binding components of the waterpurification pack 12 thus ensure removal of particulate, ionic andorganic contaminants from the diluent as it passes through the pack 12.Endotoxins, including organic matter such as cell walls from deadbacteria, can be particularly toxic. Highly purified diluent, sufficientto comply with or exceed FDA and U.S. Pharmacopoeia water qualitystandards for “sterile water for injection,” exits the outlet 24, butwithout the need for reverse osmosis.

With reference to FIG. 1 again, purified diluent then passes from thewater purification pack 12 to a collection/delivery device. As notedabove, in one embodiment, the downstream device can comprise a simplystorage container, such as a plastic bag. In the illustrated embodiment,the storage/delivery device comprises the reagent cartridge 14.Desirably, the downstream storage/delivery device is irreversibly fixedto the water pack outlet 24, either integrally or through a lockingmechanism.

FIGS. 3-5 illustrate dissolution of dry reagent 64 as diluent passesthrough the single-bed reagent cartridge 14 for the peritoneal dialysis.While illustrated cross-sectionally, it will be understood that thepreferred transparent or translucent housing 50 enables the user tosimilarly observe dissolution of the reagent bed 64 as solvent ordiluent passes therethrough. Additionally, the user can observe whetherinsoluble precipitates are present within the reagent bed, prior toemploying the cartridge 14. Advantageously, gravitational force issufficient to draw the water through the cartridge 14.

Referring initially to FIG. 3, purified diluent enters the cartridge 14through the inlet port 52. Preferably, purified diluent is fed directlyfrom the water purification pack 12. “Directly,” as used herein, doesnot preclude use of intermediate tubing, etc, but rather refers to thefact that water is purified on site immediately prior to solutionformation, rather remotely produced and shipped. It will also beunderstood, however, that the illustrated reagent cartridge will haveutility with other sources of sterile diluent.

The diluent passes through the porous inlet frit 56 and the upstreamcompression component 60. In the illustrated embodiment, the compressioncomponent 60 is a porous, open-celled foam, which readily allows diluentto pass therethrough. The diluent then passes through the upstreamreagent restraint 66 to reach the dry reagent bed 64. In addition toretaining the dry reagents in the bed 64, the frit 56 and restraint 66facilitate an even distribution of water flow across the sectional areaof the housing 50.

As the solution passes through interstitial spaces in the bed 64, thedry reagents are eroded, preferably dissolved, and carried by thediluent through the downstream reagent restraint 68, the downstreamcompression component 44 and the outlet frit 58, exiting through outlet24. The solution passes through the tube 18 into the collectionreservoir 16 (see FIG. 1) and then into the peritoneal cavity of apatient.

Referring to FIG. 4, as the reagents are dissolved, the volume of thereagent bed 64 is reduced, as can be seen from a comparison of FIG. 4with FIG. 3. The compression components 60, 62 apply continuouscompressive force on either side of the reagent bed 64. As dry reagentis dissolved, the compressive force packs the reagents close together.Such continuous packing prevents expansion of interstitial spaces as thereagent particles are dissolved. Without the compressive force, theinterstitial spaces between the reagent particles tend to expand intolarger channels within the reagent bed 64. These channels would serve asdiluent flow paths, which would permit a large volume of diluent to flowthrough the bed 64 with minimal further dissolution. Significantportions of the bed would be by-passed by these channels, anddissolution would be slow and inefficient. Applying continuouscompression to the beds minimizes this problem by continuously forcingthe reagent particles together as the bed dissolves, ensuringcontinuous, even exposure of the diluent to the reagents of the bed 64.

Though two compression components 60, 62 are preferred, thus compressingthe reagent bed 64 from two sides, it will be understood that a singlecompression component can also serve to keep the regent beds 64compacted. Moreover, though illustrated in an axial arrangement, suchthat diluent flows through the compression components 60, 62, it will beunderstood that the compression components can exert a radial force inother arrangements.

The compressive force of the preferred compression components 60, 62,exerted evenly across the housing 50, additionally aids in maintainingthe planar configuration of the reagent restraints 66, 68 on either sideof the reagent bed 64, even as the compression components 60, 62 movethe restraints inwardly. The restraints 66, 68 thus continue to form aneffective seal against the housing sidewalls, preventing dry reagentparticulates from escaping the bed 64 until dissolved.

With reference to FIG. 5, dissolution continues until the reagent bed isdepleted and the restraints 66, 68 contact one another. Diluent cancontinue to flow through the housing 50 into the reservoir 16 (FIG. 1)until the appropriate concentration of peritoneal dialysate solution isformed. For example, in the illustrated embodiment, 2 liters of diluentshould be mixed with the contents of the reagent bed 64. Accordingly, 2liters of diluent are passed through the housing 50. The contents aretypically fully dissolved by the time about 1.5 liters has passedthrough the housing, but diluent can continue to flow until theappropriate final concentration is reached in the reservoir.Alternatively, a concentrate can be first formed and independentlydiluted.

Advantageously, the illustrated apparatus and method can form peritonealdialysis solution simply by passing water through the cartridge 50,without complex or time consuming mixing equipment. The solution canthus be formed on-site, immediately prior to delivery to the peritonealcavity, such that the dialysate need not be shipped or stored insolution form. Accordingly, a low acid level is possible without unduerisk of dextrose carmelization. Conventionally, a pre-formed dialysissolution formed has a pH between about 4.0 and 6.5, and the exemplaryreagent mix of Table I produces a conventional solution with pH of about5.2. Solution produced from the illustrated single-bed cartridge ofFIGS. 3-4, however, can have lower acidity, since dextrose does not sitin solution for extended periods of time. Accordingly the pH level ispreferably between about 6.0 and 7.5, more preferably about 7.0.

Referring to FIGS. 6 and 7, the double-bed reagent cartridge 14′operates in similar fashion. Purified diluent is fed to the housinginlet 52, and passes through the inlet frit 56, the upstream compressioncomponent 60, the upstream restraint 66, and into the primary reagentbed 80. Dissolution of reagents in the primary bed 80 forms a solutionwhich passes on through the first intermediate restraint 84, theintermediate compression component 88 and the second intermediaterestraint 86. Reagents in the secondary bed 82 then also dissolve intothe diluent, and the enriched solution continues on through thedownstream reagent restraint 68, the downstream compression component 62and the outlet frit 58. A complete solution thus exits the outlet port54.

As in the previous embodiment, the regent beds 80, 82 are continuallycompressed as the reagents dissolve. Use of three compression components60, 88, 62 has been found to improve dissolution by compressing each bed80, 82 from two sides. The skilled artisan will understand, however,that two compression components, in the positions of the upstream anddownstream third components, can adequately serve to keep the reagentbeds compressed enough to aid the rate of dissolution, particularly ifprovided with a high degree of elasticity. Similarly, a singleintermediate compression component, in the position of the illustratedintermediate compression component 88, can accomplish this function,while advantageously also separating the incompatible reagent beds.Additionally, the compression component need not be axially aligned withthe reagent beds, but could instead surround or be surrounded by thereagent beds, in which case the compression components would preferablybe outside the diluent flow path.

Advantageously, the illustrated embodiments provide stable, dry forms ofperitoneal dialysis solutions. Storage and transport of the reagentcartridges of the illustrated embodiments represents considerable costsavings over storage and transport of prepared peritoneal dialysatesolutions. Dry or lyophilized reagents are moreover more stable thansolution, and therefore less harmful to the patient.

While the storage and transport of dry reagents is generally recognizedas advantageous, practical application has been difficult. The describedembodiments not only provide transport and storage, but additionallyprovide integrated mechanisms to ensure complete dissolution of the dryreagents. Continuous compression of the reagent bed(s) duringdissolution, combined with the transparent windows allowing real timeviewing of the dissolution, ensure rapid, complete and verifiabledissolution of the reagents. Thus, the preferred embodiments can beutilized on site, even in the home, without requiring complex mixingand/or analytical tools.

Moreover, the illustrated embodiments facilitate a wider practicablerange of reagents. For example, physiologically compatible bicarbonatecan be employed along with calcium and magnesium. Separate storage andsolution preparation only immediately prior to administration enablesthis combination. High dextrose solutions, as appropriate for peritonealdialysis, can be employed without acidic buffers, such thatphysiologically compatible pH levels can be practically obtained,preferably between about 4.0 and 7.5, and more preferably between about6.0 and 7.5. The reagents listed in Table II produce a solution with apH of about 7.0.

The illustrated fluid purification pack 12 is also a compact,conveniently transportable device that facilitates on-site production ofinjectable quality fluid from available fluid. Advantageously, despite asmall size and low feed pressure, the pack 12 rapidly provides on-site,injectable quality water as input water flows linearly from inlet tooutlet. A permeable terminal filter 36, represents the lowest porosityelement in the pack 12. In contrast to semi-permeable, osmoticmembranes, this element facilitates this high flux at low pressureswhile still retaining extremely fine particles and toxins.

Although the foregoing invention has been described in terms of certainpreferred embodiments, other embodiments will become apparent to thoseof ordinary skill in the art in view of the disclosure herein.Accordingly, the present invention is not intended to be limited by therecitation of preferred embodiments, but is intended to be definedsolely by reference to the dependent claims.

I claim:
 1. A portable, handheld apparatus for producing injectablequality single fluid, comprising: a housing defining a fluid flow paththerethrough from an inlet port to an outlet port; a depth filtrationstage within the housing along the fluid flow path; an organicfiltration component within the housing along the fluid flow path; adeionization resin bed within the housing along the fluid flow path; anda permeable membrane within the housing along the fluid flow path, thepermeable membrane having a porosity of less than about 0.5 μm andconfigured to retain endotoxins.
 2. The apparatus of claim 1, whereinthe permeable membrane comprises a microfiltration membrane having aporosity of less than or equal to about 0.2 μm.
 3. The apparatus ofclaim 2, wherein the microfiltration membrane comprises anendotoxin-binding treatment.
 4. The apparatus of claim 3, wherein theendotoxin-binding treatment comprises a quaternary amine exchangechemistry.
 5. The apparatus of claim 4, wherein the permeable membranefurther comprises a second microfiltration membrane having a porosity ofless than or equal to about 0.22 μm and a quaternary amine exchangechemistry.
 6. The apparatus of claim 1, wherein the permeable membranecomprises an ultrafiltration membrane having a nominal cut-off porositybetween about 10,000 and 30,000 molecular weight.
 7. The apparatus ofclaim 6, wherein the ultrafiltration membrane has a nominal cut-offporosity of between about 15,000 and 25,000 molecular weight.
 8. Theapparatus of claim 1, wherein the depth filtration stage comprises atleast two particle filters having successively lower porosity from aninlet end to an outlet end of the depth filtration stage.
 9. Theapparatus of claim 8, wherein the depth filtration stage comprisessuccessive 100 μm, 40 μm, 10 μm and 1 μm particle filters.
 10. Theapparatus of claim 1, wherein the deionization resin bed comprises amixed bed of anion-exchangers and cation-exchangers.
 11. The apparatusof claim 1, wherein the permeable membrane serves as a terminal filterproximate the outlet.
 12. The apparatus of claim 1, further comprising acollection/delivery device connected to the outlet of the housing. 13.The apparatus of claim 12, wherein the housing is connected to thecollection/delivery device by an irreversible locking mechanism.
 14. Theapparatus of claim 13, wherein the collection/delivery device comprisesa reagent cartridge housing dry reagents suitable for an injectablesolution.
 15. The apparatus of claim 12, wherein the collection/deliverydevice comprises a purified water storage container connected to thehousing by way of a welded tube.
 16. The apparatus of claim 1, whereinthe housing has a length of less than about 6 inches and the fluid flowpath has a cross-section of less than about 20 square inches.
 17. Theapparatus of claim 1, wherein water passed through the housing has atotal organic content of less than about 1 ppm; conductivity of lessthan about 5.0 μSiemens; pH between about 4.5 and 7.5; fewer than about12 particles/mL of particles smaller than 10 μm; and lower than about0.025 ng/mL of endotoxins.
 18. The apparatus of claim 17, wherein waterpassed through the housing has a total organic content of less thanabout 500 ppb; conductivity of less than about 2.0 μSiemens; pH betweenabout 5.0 and 7.0; fewer than about 6 particles/mL of particles smallerthan 10 μm; and lower than about 0.025 ng/mL of endotoxins.
 19. Theapparatus of claim 1, wherein the housing has a length from the inletport to the outlet port of less than or equal to about 6 inches.
 20. Theapparatus of claim 1, wherein the housing has a length from the inletport to the outlet port and a width, perpendicular to the length, ofless than or equal to about 5 inches.
 21. A handheld water purificationpack for producing injectable quality water, comprising a containerdefining a flow-through path from an inlet to an outlet, the path havingan average cross-sectional area of less than about 20 square inches, thecontainer housing a plurality of purification elements within the path,including a permeable membrane having a porosity of no more than about0.5 μm, the plurality of purification elements providing a back-pressurelow enough to allow fluid flow therethrough of greater than about 30mL/min under a feed pressure of between about 5 psi and 10 psi.
 22. Thewater purification pack of claim 21, wherein the permeable membrane hasa porosity of no more than about 0.2 μm.
 23. The water purification packof claim 22, wherein the plurality of purification elements comprises adepth filtration stage.
 24. The water purification pack of claim 23,wherein the depth filtration stage comprises about 100 μm, 40 μm, 10 μmand 1 μm depth filtration elements.
 25. The water purification pack ofclaim 21, wherein the housing contains an inlet including an irreversibelocking mechanism proximate the outlet configured to connect with adownstream collection/delivery device.
 26. The water purification packof claim 21, wherein the plurality of purification elements furthercomprises a mixed bed of anion-exchangers and cation-exchangers.
 27. Thewater purification pack of claim 26, wherein the plurality ofpurification elements further comprises an organic adsorption stage. 28.The water purification pack of claim 21, wherein the permeable membranecomprises an ultrafiltration membrane having a nominal porosity cut-offof between 10,000 about 30,000 molecular weight.
 29. The waterpurification pack of claim 21, wherein the plurality of purificationelements provide a back-pressure low enough to allow fluid flowtherethrough at greater than about 90 mL/min under a feed pressure ofbetween about 5 psi and 10 psi.
 30. The water purification pack of claim21, wherein the container has a length from the inlet to the outlet ofless than or equal to about 6 inches.
 31. The water purification pack ofclaim 30, wherein the container has a width, perpendicular to thelength, of less than or equal to about 5 inches.